B cell dependent T cell function blocked by perinatal exposure of mice to anti-IgM antibodies

Gordon, Julius; Mitrovski, Biserka; Abikar, K.

doi:10.1016/0008-8749(89)90010-5

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…A requirement for B cells or B cell Ig early after birth for activation of particular subsets of T cells has been demonstrated previously (17,(47)(48)(49)(50). B cells can also present Ig determinants to T cells (51), and natural IgM has been shown to play a role in maturation of the immune response (52).…”

Section: Table V T Cells From B Cell-deficient Nodk Mice Induce Satmentioning

confidence: 99%

“…Normal mouse Ig given to anti-IgM treated or NOD.K null mice using the regimen that was successful in our earlier study (17) had no effect on the ability of B cell-deficient mice to develop SAT (data not shown). This suggests that B cells probably do not simply provide Ig that could promote T cell activation or selection of the T cell repertoire by various mechanisms (47)(48)(49)(50)(51)(52), unless the Ig component is an autoantibody (53) and/or is unique to NOD.H-2h4 mice. To address some of these questions, we are generating NOD.K null mice that express transgenic surface Ig ϩ B cells that do not secrete Ig (10) to provide a model in which B cells will be present at birth, but autoantibody will not be produced.…”

Section: Table V T Cells From B Cell-deficient Nodk Mice Induce Satmentioning

confidence: 99%

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Early Requirement for B Cells for Development of Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice

Braley‐Mullen

2000

The Journal of Immunology

126

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B cells are known to play an important role in the pathogenesis of several autoimmune diseases. NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) and anti-mouse thyroglobulin (MTg) autoantibodies, the levels of which correlate closely with the severity of thyroid lesions. NOD.H-2h4 mice genetically deficient in B cells (NOD.Kμnull) or rendered B cell-deficient by treatment from birth with anti-IgM develop minimal SAT. B cells were required some time in the first 4–6 wk after birth, because NOD.Kμnull or NOD.H-2h4 mice did not develop SAT when they were reconstituted with B cells as adults. The requirement for B cells was apparently not solely to produce anti-MTg autoantibodies, because passive transfer of anti-MTg Ab did not enable B cell-deficient mice to develop SAT, and mice given B cells as adults produced autoantibodies but did not develop SAT. B cell-deficient mice developed SAT if their T cells developed from bone marrow precursors in the presence of B cells. Because B cells are required early in life and their function cannot be replaced by anti-MTg autoantibodies, B cells may be required for the activation or selection of autoreactive T cells. These autoreactive T cells are apparently unable to respond to Ag if B cells are absent in the first 4–6 wk after birth.

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Section: Table V T Cells From B Cell-deficient Nodk Mice Induce Satmentioning

confidence: 99%

Section: Table V T Cells From B Cell-deficient Nodk Mice Induce Satmentioning

confidence: 99%

Early Requirement for B Cells for Development of Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice

Braley‐Mullen

2000

The Journal of Immunology

126

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“…On the other hand, there are indications that the repertoire of autoantibody-producing B cells may become selected and controlled via their Id [15,19,[34][35][36][37][38][39][40][41][42][43][44][45][46][47], since maturatiodexpansion of autoreactive B cells will be influenced by Tcells [36,37, and since the repertoire will change during postnatal maturation [37,531. Finally, there is experimental evidence to support the idea that autoreactive B cells are relevant for the coordinate development of the early immune system [15,19,38,39,54,55]. To shed more light on these alternative assumptions, we evaluated the presence and regulation of an antibody displaying degenerate specificity (Sp6) in transgenic mice as well as in normal mice after introduction of the nominal antigen.…”

Section: Introductionmentioning

confidence: 99%

Evidence for regulation of naturally activated autoreactive B cells

Zöller

Achtnich

1991

Eur J Immunol

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A large fraction of naturally activated B cells in the neonate displays degenerate specificity, including reactivity with autoantigens. Transgenic mouse models of autoreactive B cells are mainly concerned with monospecific B cells of high avidity, and the fate of naturally activated autoreactive B cells is still a matter of debate. To pursue this question further, we chose an IgM autoantibody with a recurrent idiotype (Id), i.e. Sp6, because transgenic mice expressing this IgM also were available. In a first approach monoclonal antibodies (mAb) derived from untreated, antigenically stimulated and transgenic mice were used to test whether there were indications for deletion or for Id regulation of naturally activated autoreactive B cells. Over 90% of thymus and spleen cell derived hybridomas from 6-day-old Sp6-transgenic mice were trinitrophenyl (TNP) reactive, carried the Sp6-Id and bound to a panel of self antigens, including mouse albumin. We failed to obtain B cell hybridomas from the thymus of 28-day-old Sp6-transgenic mice. Furthermore, we could not detect any mAb carrying an anti-Sp6 Id, but Sp6 did weakly bind to itself. About 25% of mAb derived from control mice displayed degenerate specificity, the majority of them also were TNP reactive. The Sp6 Id was found at a low frequency and a comparable number of mAb carried an anti-Sp6 Id. Prenatal manipulation at the antigen level (trinitrobenzenesulfonic acid treatment) led to a transient expansion of TNP- and autoreactive mAb. The number of mAb carrying the Sp6 Id was not increased, but mAb carrying an anti-Sp6 Id were observed at high frequency. Those mAb also displayed degenerate specificity. Since Sp6-transgenic mice were perfectly healthy, it is concluded that this particular autoreactive antibody of degenerate specificity cannot be harmful for the developing organism, which may possibly be due to its self-binding capacity. Furthermore, some process of down-regulation was indicated by the absence of B cells expressing the transgene in the thymus of young adult mice. Autoreactivity of untreated and prenatally antigen-treated mice was, in addition, regulated at the Id level. In particular, mAb recognizing the Id of Sp6 were significantly expanded in antigenically stimulated mice. The data were interpreted in the sense that autoreactive B cells appearing early during ontogeny were rather strictly controlled either by (functional) clonal deletion or by idiotypic connectivity.

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2,4,6‐Trinitrophenyl (TNP) responsiveness of anti‐TNP (Sp6) transgenic mice

Zöller

1991

Eur J Immunol

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Transgenic mouse models have demonstrated clonal deletion as well as clonal anergy of monospecific, high-avidity autoreactive B cell. The function and fate of naturally activated B cells, many of them displaying degenerate specificity including autoreactivity, are still a matter of debate. The question was pursued in Sp6-transgenic mice. Sp6, a monoclonal anti-2,4,6-trinitrophenyl (TNP) IgM has been shown to react with a variety of self antigens. Responsiveness of antibody-secreting B cells was followed throughout postnatal development of Sp6-transgenic mice and was related to the availability of antigen- and idiotype-specific help. Thymus as well as spleen cells of transgenic mice contained a significantly higher number of TNP-specific B cell than non-transgenic controls. In contrast to control mice, the number of TNP-specific B cells remained unchanged or decreased in thymus and spleen of transgenic mice after antigenic stimulation with TNP in T-dependent (TD) and T-independent (TI) form. Since the relative frequency of transgenic B cells was in particular diminished after repeated stimulation with TD antigen, it was examined whether limited responsiveness was linked to the available repertoire of helper T cells. Early after birth of transgenic individuals, thymic as well as splenic T cells which proliferated in response to TNP and Sp6 and provided help for B cells were found to be significantly augmented. Their number decreased rapidly during postnatal maturation and Th cells did not expand after antigenic stimulation. There was no indication that in the naive host transgenic B cells would suppress proliferation of TNP- and Sp6-specific T cells, but they did so after antigenic stimulation. Furthermore, and in contrast to B cells of non-transgenic mice, transgenic B cells were unable to present nominal antigen in a stimulatory way. The decrease in the number of B cells after antigenic stimulation indicated that autoreactive transgenic B cells may be subject to (functional) deletion under selected circumstances. In addition, idiotype- and antigen-specific help was impaired in Sp6-transgenic mice and this clearly was due to interactions with B cells expressing the immunoglobulin transgene.

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B cell dependent T cell function blocked by perinatal exposure of mice to anti-IgM antibodies

Cited by 4 publications

References 23 publications

Early Requirement for B Cells for Development of Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice

Early Requirement for B Cells for Development of Spontaneous Autoimmune Thyroiditis in NOD.H-2h4 Mice

Evidence for regulation of naturally activated autoreactive B cells

2,4,6‐Trinitrophenyl (TNP) responsiveness of anti‐TNP (Sp6) transgenic mice

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